Cell-SELEX and application research of a DNA aptamer against esophageal squamous cell carcinoma (ESCC) cell line TE-1.

Esophageal cancer is a common cancer with high morbidity and mortality that severely threatens the safety and quality of human life. The strong metastatic nature of esophageal cancer enables it to metastasize more quickly and covertly, making it difficult for current diagnostic and treatment methods to achieve efficient early screening, as well as timely and effective treatment. As a promising solution, nucleic acid aptamers, a kind of special single-stranded DNA or RNA oligonucleotide selected by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology, can specifically bind with different molecular targets. In this paper, random DNA single-stranded oligonucleotides were used as the initial library. Using TE-1 cells and HEEC cells as targets, specific binding sequences were selected by 15 rounds of the cell-SELEX method, and the aptamer sequence that binds to TE-1 cells with the most specificity was obtained and named Te4. The Te4 aptamer was further validated for binding specificity, binding affinity, type of target, in vitro cytotoxicity when conjugated with DOX(Te4-DOX), and in vivo distribution. Results of in vitro validation showed that Te4 has outstanding binding specificity with a Kd value of 51.16 ± 5.52 nM, and the target type of Te4 was preliminarily identified as a membrane protein. Furthermore, the cytotoxicity experiment showed that Te4-DOX has specific cytotoxicity towards cultured TE-1 cells. Finally, the results of the in vivo distribution experiment showed that the Te4 aptamer is able to specifically target tumor regions in nude mice, showing great potential to be applied in future diagnosis and targeted therapy of esophageal cancer.

From biogenesis to aptasensors: advancements in analysis for tumor-derived extracellular vesicles research.

Extracellular vesicles (EVs) are enclosed by a nanoscale phospholipid bilayer membrane and typically range in size from 30 to 200 nm. They contain a high concentration of specific proteins, nucleic acids, and lipids, reflecting but not identical to the composition of the parent cell. The inherent characteristics and variety of EVs give them extensive and unique advantages in the field of cancer identification and treatment. Recently, EVs have been recognized as potential tumor markers for the detection of cancer. Aptamers, which are molecules of single-stranded DNA or RNA, demonstrate remarkable specificity and affinity for their targets by adopting distinct tertiary structures. Aptamers offer various advantages over their protein counterparts, such as reduced immunogenicity, the ability for convenient large-scale synthesis, and straightforward chemical modification. In this review, we summarized EVs biogenesis, sample collection, isolation, storage and characterization, and finally provided a comprehensive survey of analysis techniques for EVs detection that are based on aptamers.

Quantitative Trait Loci Sequencing and Genetic Mapping Reveal Two Main Regulatory Genes for Stem Color in Wax Gourds.

Stem color is an important agronomic trait of wax gourds. However, its regulatory genes have not been identified. In this study, 105 inbred lines constructed from two parents (GX-71 and MY-1) were sequenced and quantitative trait loci sequencing was used to mine the genes that regulate stem color in wax gourds. The results identified two quantitative trait loci related to stem color, qSC5 and qSC12, located on Chr05 (11,134,567-16,459,268) and Chr12 (74,618,168-75,712,335), respectively. The qSC5 had a phenotypic variation rate of 36.9% and a maximum limit of detection of 16.9. And the qSC12 had a phenotypic variation rate of 20.9%, and a maximum limit of detection of 11.2. Bch05G003950 (named BchAPRR2) and Bch12G020400 were identified as candidate genes involved in stem color regulation in wax gourds. The chlorophyll content and expression of BchAPRR2 and Bch12G020400 were significantly higher in green-stemmed wax gourds than in white-stemmed ones. Therefore, BchAPRR2 and Bch12G020400 were considered the main and secondary regulatory genes for wax gourd stem color, respectively. Finally, InDel markers closely linked to BchAPRR2 were developed to validate the prediction of wax gourd stem color traits in 55 germplasm lines, with an accuracy of 81.8%. These findings lay the foundation for exploring the genetic regulation of wax gourd stem color and future research on wax gourd breeding.

Case report: TP53 c.848G>A germline mutation as a possible screening target at initial diagnosis for acute lymphoblastic leukemia.

BACKGROUD: Li-Fraumeni syndrome is a hereditary tumor syndrome characterized by an elevated risk of malignancy, particularly acute lymphoblastic leukemia (ALL), which can be caused by the heterozygous germline mutation. TP53 gene germline mutation is considered a potential risk factor and crucial prognostic parameter for acute leukemia development and diagnosis, but rarely occurs in adults, and its specific pathogenic significance in acute leukemia is unclear. CASE PRESENTATION: We describes a case of a 45-year-old woman diagnosed with ALL. Whole-exome sequencing approach identified one of the TP53 germline mutations from her bone marrow sample with possible pathogenic significance, c.848G>A (p.Arg283His) heterozygous missense mutation located on exon 8, which was further verified in her hair, oral mucous and nail samples. Family pedigree screening revealed that the same TP53 genetic variant was present in the patient's father and non-donor son, whereas not in the donor. Digital PCR observed that this point mutation frequency dropped post-transplantation but remained low during maintenance therapy when the patient was leukemia-free. CONCLUSION: This suspected Li-Fraumeni syndrome case report with a likely pathogenic heterozygous TP53 variant expands the cancer genetic spectrum. Screening her family members for mutations facilitates identifying the optimal relative donor and avoids unnecessary treatment by monitoring TP53 germline mutations for minimal residual disease following hematopoietic stem cell transplantation. Its potential roles in hematological malignant tumor development and clinical pathogenic implications necessitate further probing.

Unraveling the Health Benefits and Mechanisms of Time-Restricted Feeding: Beyond Caloric Restriction.

Time-restricted feeding (TRF) is a lifestyle intervention that aims to maintain a consistent daily cycle of feeding and fasting to support robust circadian rhythms. Recently, it has gained scientific, medical, and public attention due to its potential to enhance body composition, extend lifespan, and improve overall health, as well as induce autophagy and alleviate symptoms of diseases like cardiovascular diseases, type 2 diabetes, neurodegenerative diseases, cancer, and ischemic injury. However, there is still considerable debate on the primary factors that contribute to the health benefits of TRF. Despite not imposing strict limitations on calorie intake, TRF consistently led to reductions in calorie intake. Therefore, while some studies suggest that the health benefits of TRF are primarily due to caloric restriction (CR), others argue that the key advantages of TRF arise not only from CR but also from factors like the duration of fasting, the timing of the feeding period, and alignment with circadian rhythms. To elucidate the roles and mechanisms of TRF beyond CR, this review incorporates TRF studies that did not use CR, as well as TRF studies with equivalent energy intake to CR, which addresses the previous lack of comprehensive research on TRF without CR and provides a framework for future research directions.

Aptamer Functionalized Hypoxia-potentiating Agent and Hypoxia-inducible Factor Inhibitor Combined with Hypoxia-activated Prodrug for Enhanced Tumor Therapy.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. Hypoxia-activated prodrugs (HAPs) have shown promise as potential therapeutic agents for TNBC. While increasing hypoxia levels may promote the HAP activation, it raises concerns regarding HIF1α-dependent drug resistance. It is desirable to develop a targeted approach that enhances tumor hypoxia for HAP activation without promoting HIF1α-dependent drug resistance in TNBC treatment. Herein, we proposed a multi-responsive carrier-free self-assembled nanomedicine named AQ4N@CA4T1ASO. This nanomedicine first targeted tumors by the TNBC-targeting aptamers (T1), and then disassembled in the reductive and acidic conditions within tumors. The released Combretastatin 4 (CA4) could exacerbate hypoxia, thereby promoting the conversion of inactive Banoxantrone (AQ4N) to its active form, AQ4. Simultaneously, the released antisense oligonucleotide (ASO) could attenuate hypoxia-induced HIF1α mRNA expression, thereby sensitizing the tumor to chemotherapy. Overall, this smart nanomedicine represents a profound targeted therapy strategy, combining "hypoxia-potentiating, hypoxia-activated, chemo-sensitization" approaches for TNBC treatment. In vivo study demonstrated significant suppression of tumor growth, highlighting the promising potential of this nanomedicine for future clinical translation.

Squaramide-catalyzed enantioselective Michael addition of nitromethane to 2-enoylazaarenes: synthesis of chiral azaarene-containing γ-nitroketones.

Bifunctional chiral squaramide-catalyzed highly enantioselective Michael addition of nitromethane to diverse 2-enoylazaarenes was successfully performed. This protocol provided a set of chiral azaarene-containing γ-nitroketones with up to 98% yield and 98% ee in a solvent-free catalytic system under mild conditions. Furthermore, gram-scale synthetic utility was also showcased.

Cross-sectional study of the association between burnout and work overload and work-life imbalance among medical personnel in Liaoning, China: role of specialty.

OBJECTIVES: Burnout is common among medical personnel in China and may be related to excessive and persistent work-related stressors by different specialties. The aims of this study were to assess the prevalence of burnout, work overload and work-life imbalance according to different specialties and to explore the effect of specialty, work overload and work-life imbalance on burnout among medical personnel. DESIGN: A cross-sectional study. SETTING: This study was conducted in 1 tertiary general public hospital, 2 secondary general hospitals and 10 community health service stations in Liaoning, China. PARTICIPANTS: A total of 3299 medical personnel participated in the study. METHODS: We used the 15-item Chinese version of the Maslach Burnout Inventory General Survey (MBI-GS) to measure burnout. Multivariable logistic regression models were used to explore the association between medical specialty, work overload, work-life imbalance and burnout. RESULTS: 3299 medical personnel were included in this study. The prevalence of burnout, severe burnout, work overload and work-life imbalance were 88.7%, 13.6%, 23.4% and 23.2%, respectively. Compared with medical personnel in internal medicine, working in obstetrics and gynaecology (OR=0.61, 95% CI 0.38, 0.99) and management (OR=0.45, 95% CI 0.28, 0.72) was significantly associated with burnout, and working in ICU （Intensive Care Unit）(OR=2.48, 95% CI 1.07, 5.73), surgery (OR=1.66, 95% CI 1.18, 2.35) and paediatrics (OR=0.24, 95% CI 0.07, 0.81) was significantly associated with severe burnout. Work overload and work-life imbalance were associated with higher ORs for burnout (OR=1.64, 95% CI 1.16, 2.32; OR=2.79, 95% CI 1.84, 4.24) and severe burnout (OR=4.33, 95% CI 3.43, 5.46; OR=3.35, 95% CI 2.64, 4.24). CONCLUSIONS: Burnout, work overload and work-life imbalance were prevalent among Chinese medical personnel but varied considerably by clinical specialty. Burnout may be reduced by decreasing work overload and promoting work-life balance across different specialties.

Association of the serum levels of saturated fatty acids and mild cognitive impairment: a cross-sectional study.

OBJECTIVES: To investigate the association of serum saturated fatty acids (SFAs) and prevalent mild cognitive impairment (MCI) among middle-aged and elderly Chinese. METHODS: A total of 607 Chinese adults aged at least 45 years were included in the baseline survey of The Lifestyle and Healthy Aging of Chinese Square Dancer Study. Serum concentrations of individual SFAs including 6 even-chain SFAs (C14:0, C16:0, C18:0, C20:0, C22:0, and C24:0) and 4 odd-chain SFAs (C15:0, C17:0, C21:0, and C23:0), were quantified by Gas chromatography system with a mass spectrometer. According to Petersen's criteria, prevalent MCI was diagnosed by neurologists through uniformed neuropsychological tests, including trail-making test-part B (TMT-B), auditory verbal learning test (AVLT), digit symbol substitution test (DSST), and verbal fluency test (VFT). RESULTS: The median age was 62 years with an interquartile range of 57.0 to 67.0 years, and 86 (14.17%) participants were living with MCI. Higher levels of either even-chain or odd-chain individual SFAs were associated with the higher odds of MCI, and their odds ratios (ORs) and 95% confidence intervals (95%CIs) were 2.054 (1.012 to 4.171) for C14:0, 2.246 (1.061 to 4.755) for C16:0, 2.789 (1.321 to 5.886) for C18:0, and 2.329 (1.136 to 4.778) for C15:0, and 2.761 (1.310 to 5.820) for C17:0, respectively. CONCLUSIONS: The serum concentration of SFAs was positively related to the odds of MCI in middle-aged and elderly adults. Determining the link between SFAs profiles and MCI may inform a better understanding of the potential role of saturated fat intake on cognitive function.

Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

Recent Advances in and Application of Fluorescent Microspheres for Multiple Nucleic Acid Detection.

Traditional single nucleic acid assays can only detect one target while multiple nucleic acid assays can detect multiple targets simultaneously, providing comprehensive and accurate information. Fluorescent microspheres in multiplexed nucleic acid detection offer high sensitivity, specificity, multiplexing, flexibility, and scalability advantages, enabling precise, real-time results and supporting clinical diagnosis and research. However, multiplexed assays face challenges like complexity, costs, and sample handling issues. The review explores the recent advancements and applications of fluorescent microspheres in multiple nucleic acid detection. It discusses the versatility of fluorescent microspheres in various fields, such as disease diagnosis, drug screening, and personalized medicine. The review highlights the possibility of adjusting the performance of fluorescent microspheres by modifying concentrations and carrier forms, allowing for tailored applications. It emphasizes the potential of fluorescent microsphere technology in revolutionizing nucleic acid detection and advancing health, disease treatment, and medical research.

Akkermansia muciniphila isolated from forest musk deer ameliorates diarrhea in mice via modification of gut microbiota.

BACKGROUND: The forest musk deer, a rare fauna species found in China, is famous for its musk secretion which is used in selected Traditional Chinese medicines. However, over-hunting has led to musk deer becoming an endangered species, and their survival is also greatly challenged by various high incidence and high mortality respiratory and intestinal diseases such as septic pneumonia and enteritis. Accumulating evidence has demonstrated that Akkermannia muciniphila (AKK) is a promising probiotic, and we wondered whether AKK could be used as a food additive in animal breeding programmes to help prevent intestinal diseases. METHODS: We isolated one AKK strain from musk deer feces (AKK-D) using an improved enrichment medium combined with real-time PCR. After confirmation by 16S rRNA gene sequencing, a series of in vitro tests was conducted to evaluate the probiotic effects of AKK-D by assessing its reproductive capability, simulated gastrointestinal fluid tolerance, acid and bile salt resistance, self-aggregation ability, hydrophobicity, antibiotic sensitivity, hemolysis, harmful metabolite production, biofilm formation ability, and bacterial adhesion to gastrointestinal mucosa. RESULTS: The AKK-D strain has a probiotic function similar to that of the standard strain in humans (AKK-H). An in vivo study found that AKK-D significantly ameliorated symptoms in the enterotoxigenic Escherichia coli (ETEC)-induced murine diarrhea model. AKK-D improved organ damage, inhibited inflammatory responses, and improved intestinal barrier permeability. Additionally, AKK-D promoted the reconstitution and maintenance of the homeostasis of gut microflora, as indicated by the fact that AKK-D-treated mice showed a decrease in Bacteroidetes and an increase in the proportion of other beneficial bacteria like Muribaculaceae, Muribaculum, and unclassified f_Lachnospiaceae compared with the diarrhea model mice. CONCLUSION: Taken together, our data show that this novel AKK-D strain might be a potential probiotic for use in musk deer breeding, although further extensive systematic research is still needed.

[Establishment of Dual Fluorescent Labeled Human High Bone Metastasis 
Lung Adenocarcinoma Cell Line and Transcriptomic Characterization Analysis].

BACKGROUND: Bone is a common site for metastasis in lung adenocarcinoma, but the mechanism behind lung adenocarcinoma bone metastasis is still unclear. And currently, there is a lack of easily traceable and stable lung adenocarcinoma bone metastasis cell models, which limits the research on the mechanism of lung adenocarcinoma bone metastasis. The establishment of human lung adenocarcinoma cell line that are highly metastatic to bone, labeled with green fluorescent proteins (GFP) and fireflies luciferase (LUC), along with transcriptomic characterization, would be beneficial for research on lung adenocarcinoma bone metastasis and provide new experimental methods. METHODS: The human lung adenocarcinoma cell line A549-GFP-LUC was injected into nude mice via the left ventricle to construct a bone metastasis model, and was domesticated in vivo for three consecutive times to obtain the human high bone metastasis lung adenocarcinoma cell line A549-GFP-LUC-BM3; cell counting kit-8 (CCK-8), colony formation assay, scratch wound assays, Transwell assay and Western blot were used to compare the proliferation and invasion abilities of A549-GFP-LUC-BM3 with the parental cells. A549-GFP-LUC-BM3 cells and parental cells were further analyzed by transcriptomic sequencing. RESULTS: Human high-bone metastatic lung adenocarcinoma cells A549-GFP-LUC-BM3 was successfully established. Compared to parental cells, this cells exhibited a significantly higher incidence of bone metastasis and enhanced in vitro proliferation, migration, and invasion abilities. Transcriptomic sequencing results revealed that the A549-GFP-LUC-BM3 cell line had 2954 differentially expressed genes compared to the parental cells, with 1021 genes up-regulated and 1933 genes down-regulated. Gene Ontology (GO) functional enrichment analysis indicated that the differentially expressed genes were primarily localized in cellular components such as the cell periphery. The molecular functions identified as significantly enriched included signaling receptor activity, calcium ion binding, and extracellular matrix structural constituent. Additionally, the biological processes found to be enriched were cell adhesion and biological adhesion. The enrichment analysis conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the differentially expressed genes were primarily involved in the metabolism of xenobiotics by cytochrome P450, retinol metabolism, drug metabolism-cytochrome P450, cell adhesion molecules, steroid hormone biosynthesis, and the nuclear factor kappa B (NF-κB) signaling pathway. CONCLUSIONS: The highly bone-metastatic human lung adenocarcinoma cell line with GFP and luciferase double labeling was successfully established. The biological behavior and transcriptome sequencing of the cell line suggest that it has a high bone-metastatic potential.

Effect of free and bound proanthocyanidins from Chinese quince on heterocyclic aromatic amine formation and quality in fried chicken.

The abilities of Chinese quince free proanthocyanidins (FP) and bound proanthocyanidins (BP) at different levels (0.1%, 0.15%, and 0.3%) to mitigate heterocyclic aromatic amine (HAA) formation in fried chicken patties were investigated for the first time and compared with vitamin C (Vc). FP and BP reduced HAAs in a dose-dependent manner. Significantly, high concentrations of FP (0.3%) resulted in a reduction of PhIP, harman, and norharman levels by 59.84%, 22.91%, and 38.21%, respectively, in chicken patties. The addition of proanthocyanidins significantly (p < 0.05) reduced the weight loss of fried chicken patties. Furthermore, a positive correlation was observed among pH, weight loss, and total HAA formation in all three groups (FP, BP, and Vc). Multivariate analysis showed that FP had a more pronounced effect than BP from the perspective of enhancing the quality of fried chicken patties and reducing the formation of HAAs. These results indicate that proanthocyanidins, both BP and FP, but especially FP, from Chinese quince can inhibit the formation of carcinogenic HAAs when added to protein-rich foods that are subsequently fried.

Chinese Healthcare Workers' Knowledge, Attitudes, and Practices in Diabetic Kidney Management: A Multi-Centered Cross-Sectional Study.

Background: Given the importance of diabetic kidney disease (DKD) management, this study aims to explore the knowledge, attitudes, and practices in disease management demonstrated by healthcare workers from the nephrology department. Materials and Methods: This study is a multi-centered cross-sectional study, and adopts snowball sampling, with 530 healthcare workers being recruited to complete a questionnaire covering areas such as demographic characteristics, knowledge, attitude, and practices (KAP) of DKD management. This data was analyzed using descriptive statistics and binary logistics analysis. Results: In this study, 530 healthcare workers were studied, including 94 doctors and 436 nurses. The participants were mainly from general tertiary hospitals in 14 provinces. For Chinese nurse, the results indicate that both poor knowledge level (Odds Ratio (OR) =0.63, 95% Confidence Interval (CI): 0.42-0.94) and having experience in further medical training in nephrology (OR=1.92, 95% CI: 1.20-3.08) are associated with the practice levels. For Chinese doctors, having not experience in further medical training in nephrology (OR=0.36, 95% CI: 0.15-0.83) are associated with their practice levels. Conclusion: In summary, Chinese doctors and nurses in this study showed positive attitudes towards DKD management, but their knowledge and practical skills were lacking. This underscores a notable gap in achieving optimal DKD care. Notably, nurses' knowledge influenced their management practices, and additional nephrology training correlated with better engagement. To improve patient care, enhancing nephrology healthcare professional training and addressing knowledge-practice disparities are recommended.

Exploration of new models for primary dysmenorrhea treatment: low-power visible-light-activated photodynamic therapy and oral contraceptives.

Background: Primary dysmenorrhea (PD) is one of the most common reasons that affect the life quality of women during childbearing age. This research aims to explore the efficacy and curative effect characteristics of oral contraceptives and low-power visible-light-activated photodynamic therapy (PDT). Besides investigating the possible mechanism of PDT, we expected to find a treatment model with better efficacy and fewer side effects. Method: It was a multicenter, randomized, parallel-controlled study. Eligible participants were randomly assigned to three groups: placebo group, oral contraceptive (Marvelon) group, and the PDT group. They were treated continuously for three menstrual cycles and followed up for two cycles after treatment. The scores of the visual analog scale (VAS) and the concentration of pain-related small molecules in blood before and after treatment were recorded in each group, which can evaluate the therapeutic characteristics of different treatments. Result: Both Marvelon and PDT were effective. The effect of Marvelon appears quickly which can significantly relieve symptoms at the beginning, while PDT shows a relatively slow role. There was no significant difference in the final efficacy two cycles after treatment. The therapeutic effect was achieved by reducing the concentrations of prostaglandin 2 (PGE2) and endothelin (ET) in the blood. Conclusion: Marvelon and PDT are effective methods for the treatment of PD. The long-term efficacy of the two is similar, while the therapeutic characteristics and the side effects are different. Patients can choose the suitable way according to their individual needs.

A retrospective study of an irradiation-based conditioning regimen and chidamide maintenance therapy in T-ALL/LBL.

OBJECTIVES: T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) are highly malignant and aggressive hematologic tumors for which there is no standard first-line treatment. Chidamide, a novel histone deacetylase inhibitor, shows great promise. We assessed the efficacy and safety of an irradiation-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and post-transplantation chidamide maintenance in patients with T-ALL/LBL. METHODS: We retrospectively analyzed the clinical data of six patients with T-ALL/LBL who underwent allo-HSCT with a radiotherapy-containing pretreatment regimen and post-transplant chidamide maintenance therapy. The endpoints were relapse, graft-versus-host disease (GVHD), transplant-related mortality (TRM), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). RESULTS: All of the patients had uneventful post-transplant hematopoietic reconstitution, and all achieved complete molecular remission within 30 days. All six patients survived, and two relapsed with a median relapse time of 828.5 (170-1335) days. The 1-year OS rate was 100%, the 2-year PFS rate was 66.7%, and the TRM rate was 0%. After transplantation, two patients developed grade I-II acute GVHD (2/6); grade III-IV acute and chronic GVHD were not observed. The most common AEs following chidamide administration were hematological AEs, which occurred to varying degrees in all patients; liver function abnormalities occurred in two patients (grade 2), and symptoms of malaise occurred in one patient (grade 1). CONCLUSION: Chidamide maintenance therapy after T-ALL/LBL transplantation is safe, but the efficacy needs to be further investigated.

The use of antibiotics in the early stage of acute exacerbation of chronic obstructive pulmonary disease in patients without obvious signs of infection: a multicenter, randomized, parallel-controlled study.

Introduction: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence and mortality. In some acute exacerbations of COPD (AECOPD) in patients with no obvious signs of infection, early antibiotic treatment seems to clinically improve the disease, but more studies are needed to determine the prognostic impact of antibiotic treatment in AECOPD patients with no obvious signs of infection. Purpose: To clarify the impact of antibiotic treatment on the short-term and long-term prognoses of AECOPD patients without obvious signs of infection. Methods: The impact of the two treatment methods on the prognosis of patients was compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, parallel-controlled clinical trial was conducted in a department of respiratory and critical care medicine in Central China. All patients met the inclusion criteria for AECOPD, and the patients were randomly assigned to the antibiotic group or the nonantibiotic group at a 1:1 ratio. Patients in the antibiotic group were given moxifloxacin 400 mg/day intravenously for 7 days. Patients in the nonantibiotic group were intravenously injected with the same amount of normal saline as the amount of moxifloxacin given to those in the antibiotic group for 7 days. Results: There were 406 patients in the antibiotic group and 410 patients in the nonantibiotic group. During the short-term and long-term follow-ups, the acute exacerbation frequency, intensive care unit (ICU) treatment rate, mortality, and mMRC and CAT scores were not significantly different between the two groups (p > 0.05). At the 180- and 360-day follow-ups, the forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups (p > 0.05). The 30-day readmission rate was significantly lower in the antibiotic group than in the nonantibiotic group (p < 0.05). The time from discharge to the first acute exacerbation was not significantly different between the two groups (p > 0.05). The length of the first hospital stay after discharge was significantly lower in the antibiotic group (5.84 days) than in the nonantibiotic group (6.75 days) (p < 0.05). At the 30-day follow-up, the acute exacerbation frequency, age, C-reactive protein (CRP) level, and sputum viscosity were significantly greater in the nonantibiotic group than in the antibiotic group (p < 0.05). In addition, according to the receiver operating characteristic (ROC) analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly greater in COPD patients aged >62.5 years, with a CRP level >12.56 mg/L or with a sputum viscosity >III, in the nonantibiotic group than in those in the antibiotic group, suggesting that the short-term prognosis was poor. Conclusion: Patients who are >62.5 years of age, have a CRP concentration >12.56 mg/L, or have a sputum viscosity >III without obvious signs of infection should be treated with antibiotics to improve their short-term prognosis. Clinical Trial Registration: (https://www.chictr.org.cn), (ChiCTR1800018921).

Association of aquatic food consumption, long-chain polyunsaturated n-3 fatty acid intake, and blood mercury levels with cognitive function in middle-aged and older adults.

BACKGROUND & AIMS: Aquatic food is rich in nutrients which benefit the human brain and cognitive health; however, concerns about heavy metal accumulation in aquatic food remain. This study evaluated the associations between aquatic food consumption, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) intake, and blood mercury levels with cognition in middle-aged and older adults. METHODS: This cross-sectional study used baseline data from the Lifestyle and Healthy Aging of Chinese Square Dancer Study. Aquatic food consumption and LC n-3 PUFAs intake were obtained from a food frequency questionnaire. Blood mercury levels were measured using inductively coupled plasma mass spectrometry. A composite z-score was developed to represent global cognition by averaging the z-scores for each cognitive domain. Participants with mild cognitive impairment (MCI) were diagnosed according to Petersen's criteria. Multivariate linear and logistic regression models were used to examine the association between the exposure factors and cognitive performance including cognitive scores and MCI. RESULTS: Of 2621 middle-aged and older adults, the mean (SD) age was 63.71 (5.15) years, and 85.73% were females. Compared with the lowest quartile, those in the highest quartile for aquatic food consumption were associated with higher composite z-scores (ß = 0.156, 95% CI: 0.088-0.225) and lower MCI odds (OR = 0.598, 95% CI: 0.425-0.841). A similar positive relationship between LC n-3 PUFAs intake and composite z-score and an inverse association between LC n-3 PUFAs intake and MCI were also observed. In addition, the participants in the highest quartile for blood mercury levels had higher composite z-scores than those in the lowest quartile. CONCLUSIONS: In this cross-sectional study, higher aquatic food consumption, LC n-3 PUFAs intake, and blood mercury levels were related to better cognitive function. Further studies in Chinese populations are required to confirm these findings.